XPC信使核糖核酸水平降低可能预示非小细胞肺癌患者预后不良。

Reduced XPC messenger RNA level may predict a poor outcome of patients with nonsmall cell lung cancer.

作者信息

Wu Yi-Hui, Cheng Ya-Wen, Chang Jinghua Tsai, Wu Tzu-Chin, Chen Chih-Yi, Lee Huei

机构信息

Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, Republic of China.

出版信息

Cancer. 2007 Jul 1;110(1):215-23. doi: 10.1002/cncr.22743.

DOI:10.1002/cncr.22743

PMID:17508409

Abstract

BACKGROUND

Homologous deletion of the xeroderma pigmentosum complementary group C (XPC) repair gene frequently causes lung adenocarcinoma in mice, suggesting that an XPC defect may play a critical role in lung tumorigenesis. The current study attempted to determine whether reduced XPC mRNA levels predict the clinical outcome of lung cancer patients.

METHODS

XPC, p27(kip) (cdk inhibitory protein), and S-phase kinase-associated protein (skp2) levels were evaluated by Western blot analysis in a series of lung cancer cell lines with different invasive abilities. Migration and invasive abilities were measured using a modified Boyden chamber without and with Matrigel, respectively. To test whether XPC affects cell invasive ability, XPC gene protein expression was reduced in low invasive cells by RNA interference (RNAi) and assayed with Boyden chamber. XPC mRNA levels in 126 nonsmall cell lung cancers (NSCLCs) were examined by real-time-reverse-transcriptase polymerase chain reaction (RT-PCR). The prognostic value of XPC mRNA expression was statistically analyzed by the Kaplan-Meier method and Cox proportional hazards regression.

RESULTS

The expression of XPC was reduced with increasing invasive potential in CL1-series lung cancer cell lines. When the XPC level was reduced by RNAi, cell migration and invasiveness increased markedly; the increased invasiveness may be caused by decreased expression of p27(kip) and increased expression of skp2 and E2F transcription factor 1. To determine whether reduced XPC expression was correlated with tumor aggressiveness and poor patient survival, XPC mRNA levels were evaluated by real-time RT-PCR. Kaplan-Meier analysis demonstrated that the median survival of patients with lower XPC mRNA levels was shorter compared with patients with higher XPC mRNA levels (P = .0440). Cox regression analysis further indicated that XPC mRNA level may act as an independent prognostic factor for NSCLC patients (P = .014).

CONCLUSIONS

The results of the current study suggest that reduced XPC mRNA level may constitute an independent prognostic factor for NSCLC patients.

摘要

背景

着色性干皮病互补组C（XPC）修复基因的同源缺失在小鼠中常引发肺腺癌，这表明XPC缺陷可能在肺肿瘤发生中起关键作用。当前研究试图确定XPC mRNA水平降低是否可预测肺癌患者的临床结局。

方法

通过蛋白质免疫印迹分析评估一系列具有不同侵袭能力的肺癌细胞系中的XPC、p27（kip）（细胞周期蛋白依赖性激酶抑制蛋白）和S期激酶相关蛋白（skp2）水平。分别使用改良的无基质胶和有基质胶的博伊登小室测量迁移和侵袭能力。为了测试XPC是否影响细胞侵袭能力，通过RNA干扰（RNAi）降低低侵袭性细胞中的XPC基因蛋白表达，并使用博伊登小室进行检测。通过实时逆转录聚合酶链反应（RT-PCR）检测126例非小细胞肺癌（NSCLC）中的XPC mRNA水平。采用Kaplan-Meier法和Cox比例风险回归对XPC mRNA表达的预后价值进行统计学分析。

结果

在CL1系列肺癌细胞系中，XPC的表达随着侵袭潜能的增加而降低。当通过RNAi降低XPC水平时，细胞迁移和侵袭能力显著增加；侵袭能力的增加可能是由于p27（kip）表达降低以及skp2和E2F转录因子1表达增加所致。为了确定XPC表达降低是否与肿瘤侵袭性和患者预后不良相关，通过实时RT-PCR评估XPC mRNA水平。Kaplan-Meier分析表明，XPC mRNA水平较低的患者的中位生存期比XPC mRNA水平较高的患者短（P = 0.0440）。Cox回归分析进一步表明，XPC mRNA水平可能是NSCLC患者的独立预后因素（P = 0.014）。